A nuclear lncRNA Linc00839 as a Myc target to promote breast cancer chemoresistance via PI3K/AKT signaling pathway
0301 basic medicine
Gene Expression Profiling
Genes, myc
Breast Neoplasms
Original Articles
Xenograft Model Antitumor Assays
3. Good health
Gene Expression Regulation, Neoplastic
Disease Models, Animal
Mice
Phosphatidylinositol 3-Kinases
03 medical and health sciences
Drug Resistance, Neoplasm
Cell Line, Tumor
Animals
Humans
Female
RNA Interference
RNA, Long Noncoding
Proto-Oncogene Proteins c-akt
In Situ Hybridization, Fluorescence
Cell Proliferation
Signal Transduction
DOI:
10.1111/cas.14555
Publication Date:
2020-07-03T15:38:19Z
AUTHORS (9)
ABSTRACT
AbstractChemoresistance has become a leading cause of mortality in breast cancer patients and is one of the major obstacles for improving the clinical outcome. Long noncoding RNAs play important roles in breast cancer tumorigenesis and chemoresistance. However, the involvement and regulation of lncRNAs in breast cancer chemoresistance are not completely understood. Here, we reported that Linc00839 was localized in the nucleus and upregulated in chemoresistant breast cancer cells and tissues, and high level of Linc00839 was associated with a poor prognosis. Knockdown of Linc00839 significantly suppressed proliferation, invasion, and migration, sensitized cells to paclitaxel in vitro and inhibited transplant tumor development in vivo. Mechanistically, we found that Myc could directly bind to the promoter region of Linc00839 and activate its transcription. Furthermore, Linc00839 overexpression increased the expression of Myc and the RNA‐binding protein Lin28B and activated the PI3K/AKT signaling pathway. We also discovered that Lin28B positively interacted with Linc00839 and was upregulated in breast cancer tissues. Taken together, for the first time, we showed that Linc00839 was activated by Myc and promoted proliferation and chemoresistance in breast cancer through binding with Lin28B. These findings provide new insight into the regulatory mechanism of Linc00839 and propose a Myc/Linc00839/Lin28B feedback loop that could be used as a novel therapeutic target for breast cancer.
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CITATIONS (44)
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